One explanation for the weak relationship between neuropsychological
deficits and conventional measures of disease burden in multiple sclerosis
is that brain 'plasticity' allows adaptive reorganization of cognitive
functions to limit impairment, despite injury.

The two subject groups
had comparable performances, but a predominantly left medial prefrontal
region [Brodmann area (BA) 8/9/10] was more active during the task in patients
than in controls (corrected P < 0.001), while a right frontal region
(including BA 45 and the basal ganglia) was more active in controls than
in patients (corrected P = 0.004).

The magnitude of the differences correlated
with the normalized brain parenchymal volume, a measure of disease burden
(r = -0.72, P = 0.02).

We then tested the effects of acute administration
of rivastigmine, a central cholinesterase inhibitor, on patterns of brain
activation.

In five out of five multiple sclerosis patients there was a
relative normalization of the abnormal Stroop-associated brain activation,
although no change in the patterns of brain activation was found in any
of four healthy controls given the drug and tested in the same way.

We
suggest that recruitment of medial prefrontal cortex is a form of adaptive
brain plasticity that compensates, in part, for relative deficits in processing
related to the reduced right prefrontal cortex activity with multiple sclerosis.

This functional plasticity is modulated by cholinergic agonism and must
arise from potentially highly dynamic mechanisms such as the 'unmasking'
of latent pathways.